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Developing novel therapies that outperform the existing chemotherapeutic treatments is required for treatment-resistant ovarian clear cell carcinoma. We investigated the antitumor effect of metformin on ovarian clear cell carcinoma, enhancement of the antitumor effect by its combination with chemotherapy, and its molecular regulatory mechanism. First, we evaluated the viability of ovarian clear cell carcinoma lines using the water-soluble tetrazolium-1 assay and found that metformin suppressed cell viability. Cell viability was significantly suppressed by co-treatment with cisplatin and metformin. In contrast, co-treatment with paclitaxel and metformin showed no significant difference in viability compared with the group without metformin. Western blot analysis showed increased phosphorylation of AMP-activated protein kinase in some cell lines and suppressed phosphorylation of the mammalian target of rapamycin in a particular cell line. Flow cytometry analysis revealed a significant increase in the rate of apoptosis in the metformin-treated group and rate of cell cycle arrest at the G2/M phase in a particular cell line. These results indicated that metformin may be effective against cultured ovarian clear cell carcinoma cells, particularly in combination with cisplatin. [ABSTRACT FROM AUTHOR]

We report a case of severe Aicardi–Goutières syndrome caused by a novel homozygous RNASEH2B intronic variant, NC_000013.10(NM_024570.4):c.65-13G > A p.Glu22Valfs*5. The patient was born with pseudo-TORCH symptoms, including intracranial calcification, cataracts, and hepatosplenomegaly. Furthermore, the patient exhibited profound intellectual impairment and died at 14 months due to aspiration pneumonia accompanied by interstitial lung abnormalities. The severity of the patient's symptoms underscores the critical role of the C-terminal region of RNase H2B. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome relapse within 6 months is a known risk factor for steroid-dependent nephrotic syndrome/frequently relapsing nephrotic syndrome (SDNS/FRNS), but the risk of early development of SDNS/FRNS and initiation of immunosuppression therapy remains unknown. Methods: Patients with childhood-onset idiopathic nephrotic syndrome who had the first relapse within 6 months were enrolled. We analyzed the relationship between the time of the first relapse or the time of initial remission and incidence of SDNS/FRNS or initiation of immunosuppression therapy. Results: Forty-five patients were enrolled. Twenty out of 23 patients (87%) with the first relapse within 30 days after discontinuing initial steroid therapy experienced a second relapse within 30 days after discontinuing steroid therapy. Additionally, most patients in this group (96%) experienced a second relapse within 6 months after the onset and were diagnosed as SDNS/FRNS at this time. In this group, the incidence of SDNS/FRNS development within 6 months was 96%. In contrast, the incidence of SDNS/FRNS development within 6 months was 18% in patients with the first relapse more than 30 days after steroid discontinuation. The incidence of initiation of immunosuppressive agents within 6 months was 83% in the former group and 14% in the latter group. Conclusions: Most patients with the first relapse within 30 days after discontinuing steroid therapy developed SDNS/FRNS and were administered immunosuppressive agents within 6 months. Thus, it might be reasonable to start immunosuppression therapy in this group without waiting for the second relapse. [ABSTRACT FROM AUTHOR]

By illuminating matter with bright and intense light, researchers gain insights into material composition and properties. In the regime of extremely short wavelengths, X-ray free-electron lasers (XFELs) with exceptional peak brilliance have unveiled crucial details about the structures, dynamics and physics of various materials. Although X-ray focusing optics to enhance the intensity have progressed, achieving a single-nanometre focal spot that fully exploits the source performance remains elusive. Aberrations arising from reflective optical schemes noticeably degrade the focal spot, even in the presence of inevitably slight angular transition and pointing errors. Here we present an approach that directly forms a source image in an extremely small focal spot, achieving 7 nm focusing, in both transverse dimensions, of 9.1 keV XFELs with the extremely high intensity of 1.45 × 1022 W cm−2. This was made possible by a scheme combining concave and convex X-ray mirrors with suppressed aberrations and high angular tolerances. The attained highly intense X-rays, surpassing the previous intensity by a hundred-fold, induced the vigorous ionization of chromium, suggesting the creation of solid-density heavy bare atomic nuclei. Our results, which demonstrate the realization of stable ultraintense XFEL beams by forming demagnified source images, hold immediate significance to a wide range of research fields, including atomic, molecular and optical physics and high-energy-density sciences. Researchers focused hard X-rays from a free-electron laser down to transverse dimensions of ~7 nm × 7 nm, enabling a two-order increase in intensity of photons and yielding access to the elusive 1022 W cm−2 regime. Such intense, short-wavelength electromagnetic radiation may probe atomic, molecular and optical physics with extremely high resolution. [ABSTRACT FROM AUTHOR]

Background: Peritonitis is the leading cause of peritoneal dialysis (PD) discontinuation. However, few data concern risk factors of peritonitis development and catheter removal caused by treatment failure in pediatric patients. Methods: This single-center, retrospective study analyzed data from pediatric patients who underwent chronic PD between March 2002 and June 2022. The incidence rates of peritonitis by the person-year method were calculated, and they were stratified by patient age groups. Risk factors for peritonitis development and catheter removal were also analyzed by multivariate analysis using logistic regression model. Results: Ninety patients were enrolled, and 62 peritonitis episodes were observed in 41 (46%) patients. The incidence rate of peritonitis was 0.21 episodes per patient-year, which was the highest in children aged under 2 years old (0.26 episodes per patient-year). Moreover, 44 (71%) cases were successfully cured by antibiotics alone, although 17 (27%) cases required catheter removal, and 4 (6%) cases transitioned to chronic hemodialysis because of peritoneal dysfunction. One patient died. The risk factor for peritonitis development and catheter removal caused by treatment failure was PD insertion at under 2 years old (odds ratio = 2.5; P = 0.04) and Pseudomonas aeruginosa (odds ratio = 11.0; P = 0.04) in the multivariate analysis. P. aeruginosa was also a risk factor for difficulty in re-initiating PD (P = 0.004). Conclusions: The incidence rate of peritonitis was the highest in children under 2 years old. P. aeruginosa peritonitis is a risk factor for catheter removal and peritoneal dysfunction. [ABSTRACT FROM AUTHOR]

To investigate the impact of sagging correction calibration errors in radiotherapy software on image matching. Three software applications were used, with and without a polymethyl methacrylate rod supporting the ball bearings (BB). The calibration error for sagging correction across nine flex maps (FMs) was determined by shifting the BB positions along the Left–Right (LR), Gun–Target (GT), and Up–Down (UD) directions from the reference point. Lucy and pelvic phantom cone-beam computed tomography (CBCT) images underwent auto-matching after modifying each FM. Image deformation was assessed in orthogonal CBCT planes, and the correlations among BB shift magnitude, deformation vector value, and differences in auto-matching were analyzed. The average difference in analysis results among the three softwares for the Winston–Lutz test was within 0.1 mm. The determination coefficients (R2) between the BB shift amount and Lucy phantom matching error in each FM were 0.99, 0.99, and 1.00 in the LR-, GT-, and UD-directions, respectively. The pelvis phantom demonstrated no cross-correlation in the GT direction during auto-matching error evaluation using each FM. The correlation coefficient (r) between the BB shift and the deformation vector value was 0.95 on average for all image planes. Slight differences were observed among software in the evaluation of the Winston–Lutz test. The sagging correction calibration error in the radiotherapy imaging system was caused by an auto-matching error of the phantom and deformation of CBCT images. [ABSTRACT FROM AUTHOR]

Background: Despite adverse events associated with the long-term use of immunosuppressants, their long-term discontinuation remains challenging in children with idiopathic nephrotic syndrome. Relapse and resumption of immunosuppressants after discontinuation and associated risk factors were analyzed. Methods: This single-center retrospective cohort study included children with frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS) or steroid-resistant nephrotic syndrome (SRNS) who initiated immunosuppressant treatment between 2010 and 2020. Patients treated with immunosuppressants for less than two years, those with genetic SRNS, and those with continuation of immunosuppressants were excluded. Results: Sixty-eight patients with FRNS/SDNS or SRNS discontinued immunosuppressants. Discontinuation of immunosuppressants was more frequently tried in patients with less relapse on initial immunosuppressants and less rituximab administration. Of 68 patients who discontinued immunosuppressants, 45 (66%) relapsed and 31 (46%) resumed immunosuppressants with a median follow-up of 39.8 months (IQR 24.6–71.2 months) after discontinuation. The relapse-free survival rates were 40.0%, 35.3%, and 35.3% in 1, 2, and 3 years from discontinuation of immunosuppressants, respectively. Relapse on initial immunosuppressants (HR 2.038, 95%CI 1.006–4.128, P = 0.048) and the relapse-free interval before discontinuation of immunosuppressants (HR 0.971, 95%CI 0.944–0.998, P = 0.037) were significant risk factors associated with relapse after the discontinuation of immunosuppressants, adjusting for sex, age at immunosuppressant treatment initiation, SRNS, and rituximab use. Conclusions: Long-term discontinuation of immunosuppressants can be feasible in patients without a relapse on initial immunosuppressants, those with longer relapse-free interval before discontinuation of immunosuppressants, and those without a relapse for one year after discontinuation of immunosuppressants. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Mitochondrial diseases are mainly caused by dysfunction of mitochondrial respiratory chain complexes and have a variety of genetic variants or phenotypes. There are only a few approved treatments, and fundamental therapies are yet to be developed. Leigh syndrome (LS) is the most severe type of progressive encephalopathy. We previously reported that apomorphine, an anti- "off" agent for Parkinson's disease, has cell-protective activity in patient-derived skin fibroblasts in addition to strong dopamine agonist effect. We obtained 26 apomorphine analogs, synthesized 20 apomorphine derivatives, and determined their anti-cell death effect, dopamine agonist activity, and effects on the mitochondrial function. We found three novel apomorphine derivatives with an active hydroxy group at position 11 of the aporphine framework, with a high anti-cell death effect without emetic dopamine agonist activity. These synthetic aporphine alkaloids are potent therapeutics for mitochondrial diseases without emetic side effects and have the potential to overcome the low bioavailability of apomorphine. Moreover, they have high anti-ferroptotic activity and therefore have potential as a therapeutic agent for diseases related to ferroptosis. [ABSTRACT FROM AUTHOR]

In this study, we investigated the composition of free amino acids and lactate (Lac) in polychaetes in river estuaries and inner bays using chromatographic techniques. Both l-amino acids and d-amino acids (d-asparagine, d-alanine (d-Ala), d-serine, d-aspartic acid, and d-proline (d-Pro)) were detected, indicating that polychaetes contain some d-amino acids. Some polychaete species exhibited notable amino acid levels, such as glycine in Capitellidae sp. and Thelepus sp., d-Pro in Glycera sp., and β-Ala in Scoletoma nipponica and Scoletoma sp.. High d-Lac levels were detected in Tylorrhynchus osawai and Hediste diadroma, (691 and 797 μmol/100 g-wet, respectively), with the d-form exceeding 98%. T. osawai was dominant in the upper tidal-sensitive zone, wherein other organisms were less abundant because of low salinity (3–8 PSU). Seasonal differences in the concentrations of components in T. osawai were observed, particularly a significant increase in d-Lac in the reproductive period. Notably, the d-Lac concentrations of T. osawai were higher upstream than downstream. Thus, d-Lac might be involved in strategies underlying adaptations to low salinity and reproductive activity. These results suggest that both the d-form of Lac and amino acids may play certain physiological roles in the life of polychaetes. [ABSTRACT FROM AUTHOR]

Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to the D5 receptor. We previously identified apomorphine as a potential therapeutic agent for mitochondrial diseases by screening a chemical library of fibroblasts from patients with mitochondrial diseases. In this study, we showed that apomorphine prevented ferroptosis in fibroblasts from various types of mitochondrial diseases as well as in normal controls. Well-known biomarkers of ferroptosis include protein markers such as prostaglandin endoperoxide synthase 2 (PTGS2), a key gene for ferroptosis-related inflammation PTGS2, lipid peroxidation, and reactive oxygen species. Our findings that apomorphine induced significant downregulation of PTSG2 and suppressed lipid peroxide to the same extent as other inhibitors of ferroptosis also indicate that apomorphine suppresses ferroptosis. To our knowledge, this is the first study to report that the anti-ferroptosis effect of apomorphine is not related to dopamine receptor agonist action and that apomorphine is a potent inhibitor of ferroptotic cell death independent of dopaminergic receptors. [ABSTRACT FROM AUTHOR]

Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a 7-month-old female patient with severe intellectual disability, epilepsy, and low levels of serum copper and ceruloplasmin. While heterozygous deletion of exons 16 and 17 of the ATP7A gene was detected in the proband, her mother, and her grandmother, only the proband suffered from Menkes disease clinically. Intriguingly, X chromosome inactivation (XCI) analysis demonstrated that the grandmother and the mother showed skewing of XCI toward the allele with the ATP7A deletion and that the proband had extremely skewed XCI toward the normal allele, resulting in exclusive expression of the pathogenic ATP7A mRNA transcripts. Expression bias analysis and recombination mapping of the X chromosome by the combination of whole genome and RNA sequencing demonstrated that meiotic recombination occurred at Xp21-p22 and Xq26-q28. Assuming that a genetic factor on the X chromosome enhanced or suppressed XCI of its allele, the factor must be on either of the two distal regions derived from her grandfather. Although we were unable to fully uncover the molecular mechanism, we concluded that unfavorable switching of skewed XCI caused Menkes disease in the proband. [ABSTRACT FROM AUTHOR]

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We present an experimental demonstration of a stable, low-loss, large X-ray cavity operating at 1.2 Å wavelength. The cavity consists of four separate high-reflectivity single crystal diamond Bragg mirrors arranged in a rectangular configuration with a round-trip distance of 14.2 m. Femtosecond X-ray pulses from an X-ray free-electron laser were coupled into the cavity via a transmission phase grating. We show that a stable mode can be maintained with the introduction of cavity focusing and measure round-trip efficiencies approaching 88%, or >96% when excluding grating and lens losses, close to the Bragg mirror theoretical performance limit. The direct observation of sustained stable X-ray circulation provides the most direct evidence to date that cavity-based X-ray free-electron lasers and other cavity-based hard X-ray systems are feasible. A low-loss cavity is shown to store X-ray laser pulses for >2.8 μs. [ABSTRACT FROM AUTHOR]

Background : Patients on peritoneal dialysis (PD) may develop PD-related complications that necessitate abdominal surgery. However, when to resume PD and how to prescribe PD fluid after surgery in pediatric patients are unknown. Methods: Patients on PD who underwent small-incision abdominal surgery between May 2006 and October 2021 were included in this retrospective observational study. The complications after surgery and characteristics of patients with PD fluid leakage were analyzed. Results: Thirty-four patients were included. They underwent 45 surgical procedures, including 23 inguinal hernia repairs, 17 PD catheter repositioning or omentectomy, and 5 others. The median time to resume PD was 1.0 (IQR, 1.0–3.0) days, and the median PD exchange volume at the initiation of PD after surgery was 25 (IQR, 20–30) ml/kg/cycle. PD-related peritonitis occurred in two patients after omentectomy and one after inguinal hernia repair. There was no PD fluid leakage or hernia recurrence among the 22 patients who had a hernia repair. Peritoneal leakage occurred in 3 of the 17 patients who had PD catheter repositioning or an omentectomy and was treated conservatively. No patients who resumed PD 3 days after small-incision abdominal surgery with less than half of PD volume had fluid leakage. Conclusions: Our findings demonstrated that PD could be resumed within 48 h of inguinal hernia repair with no PD fluid leakage or hernia recurrence in pediatric patients. In addition, resuming PD 3 days after a laparoscopic procedure with less than half of the usual dialysate volume might reduce the risk of PD fluid leakage. [ABSTRACT FROM AUTHOR]

In this note we discuss absolutely norm attaining property (A N -property in short) of the Jordan product and Lie-bracket. We propose a functional calculus for positive absolutely norm attaining operators and discuss the stability of the A N -property under the functional calculus. As a consequence we discuss the operator mean of positive A N -operators. [ABSTRACT FROM AUTHOR]

Purpose: The pathology of branch retinal vein occlusion (BRVO), a retinal circulatory disease, is related to monocular metamorphopsia-related vision impairment of the affected eyes, but the association of binocular metamorphopsia in such patients is unclear. This study aimed to examine the frequency of binocular metamorphopsia and its association with the clinical characteristics of patients with BRVO. Methods: A total of 87 patients who were treated for BRVO-associated macular edema (ME) were included in this study. At baseline and 1 and 3 months after the initiation of anti-vascular endothelial growth factor (VEGF) treatment, we quantified metamorphopsia in the affected eyes and binocular metamorphopsia using the M-CHARTS® diagnostic tool. Results: At baseline, 53 and 7 patients had metamorphopsia in the affected eyes and binocular metamorphopsia, respectively. Although the visual acuity improved significantly after the initiation of anti-VEGF treatment, the mean M-CHARTS score in the affected eyes did not change from the baseline score. At 3 months, 9 patients showed binocular metamorphopsia; it was significantly associated with metamorphopsia in the affected eyes with a 95% confidence interval of 0.021–0.122 (β = 0.306, p = 0.006). Conclusion: Metamorphopsia in the affected eyes can cause binocular metamorphopsia in patients with BRVO-ME. [ABSTRACT FROM AUTHOR]

High sensitivity of the Kβ fluorescence spectrum to electronic state is widely used to investigate spin and oxidation state of first-row transition-metal compounds. However, the complex electronic structure results in overlapping spectral features, and the interpretation may be hampered by ambiguity in resolving the spectrum into components representing different electronic states. Here, we tackle this difficulty with a nonlinear resonant inelastic X-ray scattering (RIXS) scheme, where we leverage sequential two-photon absorption to realize an inverse process of the Kβ emission, and measure the successive Kα emission. The nonlinear RIXS reveals two-dimensional (2D) Kβ-Kα fluorescence spectrum of copper metal, leading to better understanding of the spectral feature. We isolate 3d-related satellite peaks in the 2D spectrum, and find good agreement with our multiplet ligand field calculation. Our work not only advances the fluorescence spectroscopy, but opens the door to extend RIXS into the nonlinear regime. X-ray fluorescence spectroscopy is a powerful tool to investigate atomic properties. Here the authors report a two-dimensional fluorescence spectrum of copper metal using X-ray nonlinear scattering and find two-hole satellite feature resulting from atomic transitions. [ABSTRACT FROM AUTHOR]

Hyperosmotic stress activates in live cells numerous processes and also promotes intracellular protein/RNA aggregation and phase separation. However, the time course and the extent of these changes remain largely uncharacterized. To investigate dynamic changes in intracellular macromolecular crowding (MMC) induced by hyperosmotic stress in live cells, we used fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy (FCS) to quantify changes in the local environment by measuring the fluorescence lifetime and the diffusion of the monomeric enhanced green fluorescent protein (eGFP), respectively. Real-time monitoring of eGFP fluorescence lifetime showed that a faster response to environmental changes due to MMC is observed than when measuring the acceptor/donor emission ratio using the MMC-sensitive Förster resonance energy transfer sensor (GimRET). This suggests that eGFP molecular electronic states and/or collision frequency are affected by changes in the immediate surroundings due to MMC without requiring conformational changes as is the case for the GimRET sensor. Furthermore, eGFP diffusion assessed by FCS indicated higher intracellular viscosity due to increased MMC during hyperosmotic stress. Our findings reveal that changes in eGFP fluorescence lifetime and diffusion are early indicators of elevated intracellular MMC. Our approach can therefore be used to reveal in live cells short-lived transient states through which MMC builds over time, which could not be observed when measuring changes in other physical properties that occur at slower time scales. [ABSTRACT FROM AUTHOR]

The chemical order and disorder of solids have a decisive influence on the material properties. There are numerous materials exhibiting chemical order/disorder of atoms with similar X-ray atomic scattering factors and similar neutron scattering lengths. It is difficult to investigate such order/disorder hidden in the data obtained from conventional diffraction methods. Herein, we quantitatively determined the Mo/Nb order in the high ion conductor Ba7Nb4MoO20 by a technique combining resonant X-ray diffraction, solid-state nuclear magnetic resonance (NMR) and first-principle calculations. NMR provided direct evidence that Mo atoms occupy only the M2 site near the intrinsically oxygen-deficient ion-conducting layer. Resonant X-ray diffraction determined the occupancy factors of Mo atoms at the M2 and other sites to be 0.50 and 0.00, respectively. These findings provide a basis for the development of ion conductors. This combined technique would open a new avenue for in-depth investigation of the hidden chemical order/disorder in materials. Chemical order/disorder in materials can be difficult to determine for atoms with similar X-ray scattering factors and neutron scattering lengths. Here authors use resonant XRD and NMR to elucidate hidden Mo/Nb chemical order in disordered hexagonal perovskite Ba7Nb4MoO20, with Mo atoms found to be localized near the ion-conducting oxygen deficient layer. [ABSTRACT FROM AUTHOR]

Purpose: Measuring health-related quality of life (HRQOL) in various health conditions in different countries is important given the regional differences. This study employed large-scale nationwide data targeting older adults in Japan to estimate the HRQOL in the key health conditions that are the major causes of disability. Methods: Our data were derived from two survey waves (2016 and 2019 surveys) of cross-sectional data from the Japan Gerontological Evaluation Study, an ongoing nationwide study targeting functionally independent older adults in Japan. A total of 28,345 individuals from 27 of the 47 Japanese provinces were analyzed. The EuroQoL 5-dimension 5-level instrument (EQ-5D-5L) was employed to assess the HRQOL utility scores. The targeted minimum loss-based estimator with sampling weighting methods was applied to estimate the utility score in eight major health conditions, including sensory organ disease, musculoskeletal disease, oral disorders, and depressive disorders. Results: The estimated HRQOL utility score for those with the poorest health conditions in self-rated health, hearing loss, vision loss, number of remaining teeth (e.g., no teeth with no denture use), oral dysfunction, depressive symptoms, chronic low back pain, and chronic knee pain was 0.576 (95% confidence interval (CI) 0.555–0.598), 0.768 (95% CI 0.737–0.800), 0.680 (95% CI 0.662–0.699), 0.809 (95% CI 0.796–0.821), 0.776 (95% CI 0.764–0.788), 0.723 (95% CI 0.710–0.737), 0.715 (95% CI 0.690–0.739), and 0.742 (95% CI 0.722–0.763), respectively. Conclusion: We successfully provided a catalog for the HRQOL utility score in key health conditions that are the leading causes of disability among older adults. [ABSTRACT FROM AUTHOR]

We report on a patient with a distal 16.4-Mb duplication at 2q36.3-qter, who presented with severe intellectual disability, microcephaly, brachycephaly, prominent forehead, hypertelorism, prominent eyes, thin upper lip, and progenia. Copy number analysis using whole exome data detected a distal 2q duplication. This is the first report describing a distal 2q duplication at the molecular level. [ABSTRACT FROM AUTHOR]

Syrphid larvae are well-known predators of aphids; however, we sometimes observed them on onion plants with thrips and without any aphids, which intercropped with barley in our previous study. Therefore, we hypothesized that syrphid larvae fed on thrips in the onion field in the absence of aphids, their main prey. This hypothesis was tested by analyzing the prey DNA from syrphid larvae collected from onion plants intercropped with barley. We found that they preyed on three thrips species: Thrips tabaci (Lindeman), Frankliniella occidentalis (Pergande), and Anaphothrips obscurus (Müller). Moreover, we observed that syrphid larvae collected from onion plants fed on larval T. tabaci in a laboratory setting. According to COI sequencing of their genomes, the syrphid species occurred from the onion plants were Sphaerophoria macrogaster (Thomson), Melanostoma scalare (Fabricius), Melanostoma mellinum (L.), and Platycheirus pennipes (Ohara); all of them were found to prey on thrips in the prey DNA analyses. These results and observations supported the hypothesis and suggested that intercropping barley as a living mulch may become an option for enhancing the potential of native syrphid species as generalist predators in the onion fields. [ABSTRACT FROM AUTHOR]

Stable isotope ratios of nitrate (NO3−) can be used as a tool to investigate NO3− dynamics in watersheds over the world. However, most of the NO3− source analyses from watersheds using isotopes have been conducted during baseflow conditions, and more information is required on conditions during rainfall, which is a crucial period for nitrogen export to downstream ecosystems. Additionally, there is limited information regarding the sources of stable isotopes of NO3− in watersheds of Japan. We measured the nitrogen and oxygen isotopes of NO3− (δ15N–NO3− and δ18O–NO3−) in the Yasu River during baseflow and rainfall events and those from major NO3− sources in the watershed. The δ15N–NO3− exported from forests and rice paddies showed small fluctuations, while there were large fluctuations in the δ15N–NO3− exported from sewage treatment plants, suggesting the need to obtain data on δ15N–NO3− exported from sewage treatment plants. The NO3− concentrations in the Yasu River during summer baseflow were too low to be explained by the mixing of NO3− sources within the watershed, suggesting that NO3− consumption processes within the river and groundwater influence the NO3− concentrations. Furthermore, the sources of NO3− exported from the watershed differed during baseflow and rainfall, with a larger contribution of forest-derived NO3− during rainfall. Monitoring during rainfall is therefore essential to determine the sources of NO3− exported from the watershed. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is associated with worse outcomes and results in high mortality; therefore, great efforts are required to find effective treatment. In the present study, we suggested a novel strategy to treat TNBC using mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) to transform the behaviors and cellular communication of TNBC cells (BCC) with other non-cancer cells related to tumorigenesis and metastasis. Our data showed that, BCC after being internalized with EV derived from Wharton's Jelly MSC (WJ-EV) showed the impaired proliferation, stemness properties, tumorigenesis and metastasis under hypoxic conditions. Moreover, these inhibitory effects may be involved in the transfer of miRNA-125b from WJ-EV to BCC, which downregulated the expression of HIF1α and target genes related to proliferation, epithelial-mesenchymal transition, and angiogenesis. Of note, WJ-EV-internalized BCC (wBCC) showed transformed behaviors that attenuated the in vivo development and metastatic ability of TNBC, the angiogenic abilities of endothelial cells and endothelial progenitor cells and the generation of cancer-associated fibroblasts from MSC. Furthermore, wBCC generated a new EV with modified functions that contributed to the inhibitory effects on tumorigenesis and metastasis of TNBC. Taken together, our findings suggested that WJ-EV treatment is a promising therapy that results in the generation of wBCC to interrupt the cellular crosstalk in the tumor environment and inhibit the tumor progression in TNBC. [ABSTRACT FROM AUTHOR]

Background: Adverse health effects resulting from falls are a major public health concern. Although studies have identified risk factors for falls, none have examined long-term prediction of fall risk. Furthermore, recent evidence suggests that there are additional risk factors, such as psychosocial factors. Objective: In this 3-year longitudinal study, we evaluated a predictive model for risk of fall among community-dwelling older adults using machine learning methods. Design: A 3-year follow-up prospective longitudinal study (from 2010 to 2013). Setting: Twenty-four municipalities in nine of the 47 prefectures (provinces) of Japan. Participants: Community-dwelling individuals aged ≥65 years who were functionally independent at baseline (n = 61,883). Methods: The baseline survey was conducted from August 2010 to January 2012, and the follow-up survey was conducted from October to December 2013. Both surveys were conducted involving self-reported questionnaires. The measured outcome at the follow-up survey was self-reported multiple falls during the previous year. The 142 variables included in the baseline survey were regarded as candidate predictors. The random-forest-based Boruta algorithm was used to select predictors, and the eXtreme Gradient Boosting algorithm with 10 repetitions of nested k-fold cross-validation was used for modeling and model evaluation. Furthermore, we used shapley additive explanations to gain insight into the behavior of the prediction model. Key Results: Fourteen out of 142 candidate features were selected as predictors. Among these predictors, experience of falling as of the baseline survey was the most important feature, followed by self-rated health and age. Moreover, sense of coherence was newly identified as a risk factor for falls. Conclusions: This study suggests that machine learning tools can be adapted to explore new associative factors, make accurate predictions, and provide actionable insights for fall prevention strategies. [ABSTRACT FROM AUTHOR]

The paper carries out the smoothed particle hydrodynamics simulations of lubrication for the micronscale iron contact by the 20 types of the spherical solid oxide particles. The iron slabs and oxide particles of micrometer sizes are modeled by the elastic particle lattice coarse-graining and discrete element method, respectively. Motion of the iron particles is presented by the governing equations of the smoothed particle hydrodynamics approach. The interactions between the particle pairs such as iron-oxide and oxide-oxide ones are presented by the Hertz repulsive contact and van der Waals attractive noncontact forces. Furthermore, the oxide particle dissipates its kinetic energy into the environment containing it through the Stockes damping force. It is found that stability and shear of the tribofilm are the main factors influencing friction reduction in all the behaviors. The interactions between the oxide-oxide particles and between the oxide-asperity iron particles mainly contribute to formation and maintainability of the tribofilm. The oxide with the higher density or the heavier oxide particle results in the lower friction coefficient. The friction reduction also strongly depends on the water/diesel environment containing the particles; however, the relative lubrication ability among the oxides is almost independent of the environment. It is also found that in the contacts with the highly condensed situation of the oxide lubricant particles the van der Waals force can be neglected due to its very slight contribution to the detected forces and the rolling of the lubricant particles almost has no contribution to friction, in contrast to the strong influence of temperature of the environment. [ABSTRACT FROM AUTHOR]

CUX2 gene encodes a transcription factor that controls neuronal proliferation, dendrite branching and synapse formation, locating at the epilepsy-associated chromosomal region 12q24 that we previously identified by a genome-wide association study (GWAS) in Japanese population. A CUX2 recurrent de novo variant p.E590K has been described in patients with rare epileptic encephalopathies and the gene is a candidate for the locus, however the mutation may not be enough to generate the genome-wide significance in the GWAS and whether CUX2 variants appear in other types of epilepsies and physiopathological mechanisms are remained to be investigated. Here in this study, we conducted targeted sequencings of CUX2, a paralog CUX1 and its short isoform CASP harboring a unique C-terminus on 271 Japanese patients with a variety of epilepsies, and found that multiple CUX2 missense variants, other than the p.E590K, and some CASP variants including a deletion, predominantly appeared in patients with temporal lobe epilepsy (TLE). The CUX2 variants showed abnormal localization in human cell culture analysis. While wild-type CUX2 enhances dendritic arborization in fly neurons, the effect was compromised by some of the variants. Cux2- and Casp-specific knockout mice both showed high susceptibility to kainate, increased excitatory cell number in the entorhinal cortex, and significant enhancement in glutamatergic synaptic transmission to the hippocampus. CASP and CUX2 proteins physiologically bound to each other and co-expressed in excitatory neurons in brain regions including the entorhinal cortex. These results suggest that CUX2 and CASP variants contribute to the TLE pathology through a facilitation of excitatory synaptic transmission from entorhinal cortex to hippocampus. [ABSTRACT FROM AUTHOR]

Anti-vascular endothelial growth factor treatment for macular edema secondary to branch retinal vein occlusion generally provides good visual acuity (VA) improvement but may require repeated injections for years. To reduce the number of patients who suffer from avoidable VA loss caused by treatment drop-out, providing prospects of the correlation between expected vision improvement and required number of injections at the early stages of treatment may be helpful. In this post hoc analysis of the phase IV, randomized, open-label ZIPANGU study, we investigated the correlation between the data from Month 2 and Month 12 in terms of VA and required ranibizumab injection numbers. Fifty-nine patients were evaluated (ranibizumab monotherapy, 29; combination therapy, 30). In the monotherapy group, patients who received 1 and 3 injections by Month 2 received a mean total of 2.8 and 8.3 injections during the year, respectively. Data from the combination group were similar. The correlation coefficients for VA scores at Months 2 and 12 were 0.60 and 0.51 for the monotherapy and combination groups, respectively (both p < 0.01). Based on VA and injection numbers at Month 2 of treatment, physicians could provide rough prospects on patients' expected final VA and required number of injections. [ABSTRACT FROM AUTHOR]

In prostate cancer, accurate diagnosis and grade group (GG) decision based on biopsy findings are essential for determining treatment strategies. Diagnosis by experienced urological pathologists is recommended; however, their contribution to patient benefits remains unknown. Therefore, we analyzed clinicopathological information to determine the significance of reassessment by experienced urological pathologists at a high-volume institution to identify factors involved in the agreement or disagreement of biopsy and surgical GGs. In total, 1325 prostate adenocarcinomas were analyzed, and the GG was changed in 452/1325 (34.1%) cases (359 cases were upgraded, and 93 cases were downgraded). We compared the highest GG based on biopsy specimens, with the final GG based on surgical specimens of 210 cases. The agreement rate between the surgical GG performed and assessed in our institute and the highest biopsy GG assessed by an outside pathologist was 34.8% (73/210); the agreement rate increased significantly to 50% (105/210) when biopsy specimens were reevaluated in our institute (chi-square test, P < 0.01). Multivariate logistic regression analysis showed that only the length of the lesion in the positive core with the highest GG in the biopsy was a significant factor for determining the agreement between biopsy GG and surgical GG, with an odds ratio of 1.136 (95% confidence interval: 1.057–1.221; P < 0.01). Thus, reassessment by experienced urological pathologists at high-volume institutions improved the agreement rate. However, it should be noted there is a high probability of discordance between a small number of lesions or short lesions and surgical GG. [ABSTRACT FROM AUTHOR]

Bimodal behavior in the translational order of silicon's second shell in SiO2 liquid at high temperatures and high pressures has been recognized in theoretical studies, and the fraction of the S state with high tetrahedrality is considered as structural origin of the anomalous properties. However, it has not been well identified in experiment. Here we show experimental evidence of a bimodal behavior in the translational order of silicon's second shell in SiO2 glass under pressure. SiO2 glass shows tetrahedral symmetry structure with separation between the first and second shells of silicon at low pressures, which corresponds to the S state structure reported in SiO2 liquid. On the other hand, at high pressures, the silicon's second shell collapses onto the first shell, and more silicon atoms locate in the first shell. These observations indicate breaking of local tetrahedral symmetry in SiO2 glass under pressure, as well as SiO2 liquid. Understanding the structural origin of the anomalous properties of SiO2 liquid and glass at high pressures is fundamental in wide range of scientific fields. Here, the authors find experimental evidence of a bimodal behavior in the translational order of silicon's second shell and breaking of local tetrahedral symmetry in SiO2 glass under pressure. [ABSTRACT FROM AUTHOR]

Ternary polymer solar cells based on a thiazolothiazole-based polymer donor (PTzBT) and a fullerene acceptor (PC61BM) have attracted attention because they show high efficiency and stability by addition of a non-fullerene acceptor (ITIC). However, the performance improvement mechanism is not completely elucidated. Here, we show the stability improvement mechanism due to less charge accumulation in the PTzBT cells with ITIC using operando electron spin resonance from a microscopic viewpoint. We observed two correlations between device performance and number of spins (Nspin) under solar irradiation. One correlation is the decrease in short-circuit current and the Nspin increase in electrons on PC61BM and holes in PTzBT, where the ITIC addition causes the less these Nspin. The other correlation is the increase in open-circuit voltage and the Nspin decrease in holes in ZnO. These findings explain the stability improvement mechanism, showing the correlation between less charge accumulation and higher stability, which is valuable for the development of further efficient and stable polymer solar cells. [ABSTRACT FROM AUTHOR]

In this article, first, we study the spectral properties of operators which attain their norm on every reducing subspace and then we study the structure of normal and quasinormal operators in this class. At the end we give a description of paranormal operators whose adjoint is also paranormal. This gives a direct proof of the fact that an operator is normal if and only if the operator and its adjoint are paranormal. [ABSTRACT FROM AUTHOR]

Median sternotomy near an existing tracheostoma risks deep sternal wound infection after cardiac surgery. We present herein a case of acute type A aortic dissection in a patient with a permanent tracheostoma after laryngectomy. Total arch replacement with both frozen elephant trunk and extra-anatomical bypass for supra-aortic trunks was performed through T-shaped partial sternotomy, resulting in recovery without deep sternal wound infection. [ABSTRACT FROM AUTHOR]

The European hedgehog (Erinaceus europaeus) is widely distributed in Europe, from Iberia and Italy to Scandinavia, and in New Zealand. They inhabit a wide range of environments, from natural habitats to urban areas. Finland is the northern edge of the current distribution area, which has expanded from Pleistocene refugia in Europe. Finnish hedgehogs are not only found in the suburbs, but also in urban areas such as the capital city, Helsinki. However, the phylogenetic relationships to other populations and the population structure were unknown for the urban hedgehogs in Helsinki. We reconstructed a molecular phylogeny and analyzed the population structure and genetic diversity from samples of 106 hedgehogs collected around Helsinki in 2017–2019, based on partial sequences of the mitochondrial control region and cytochrome b gene as well as 11 microsatellite loci. Our phylogenetic data indicate that the Helsinki population is closely related to the Estonian population. This means that at least part of the Helsinki population originates from Estonia, due to natural expansion from glacial refugia and anthropogenic introduction for vermin control, as shown in previous reports. The microsatellite data indicated that the Helsinki population is genetically homogeneous, with low genetic diversity. This may be due to the absence of effective geographic barriers to gene flow at present, but it is also possible that the subpopulations formed by migration are concealed by the genetic uniformity resulting from founder effect of natural expansion to the northward or artificial introduction. Further study is necessary to evaluate the effect of urban fragmentation in Helsinki. [ABSTRACT FROM AUTHOR]

Biotin-responsive basal ganglia disease (BBGD) with SLC19A3 mutation was first reported in 1998, and over 30 mutations have been reported. We report a neonatal BBGD case with sudden-onset feeding difficulty and impaired consciousness. Encephalopathy resolved after the initiation of biotin and thiamine treatment. Genetic testing revealed a novel heterozygous mutation [c.384_387del, p.Tyr128fs];[c.265 A > C, p.Ser89Arg] in SLC19A3. Early treatment for BBGD is essential, especially with onset in the neonatal or early infancy period. [ABSTRACT FROM AUTHOR]

Background: There is no established view of how gastric acid suppression affects the time for gastric emptying. Vonoprazan fumarate shows potent and durable gastric acid inhibitory effects, but its effects on gastric emptying have not been studied widely. We investigated the effects of vonoprazan fumarate on gastric emptying and measured serum gastrin and plasma ghrelin levels in healthy adults. Methods: Ten participants were administered 10 mg vonoprazan fumarate daily for 14 days, then 20 mg vonoprazan fumarate daily for 14 days. The gastric emptying breath test was performed and serum gastrin levels were measured at baseline and after each medication administration period. The protocol was then repeated, with the gastric emptying breath test and serum gastrin and plasma desacyl-ghrelin levels measured at baseline and the end of the medication trial. Results: Mean serum gastrin levels increased in a dose-dependent manner [baseline: 104.7 ± 50.4, after 10 mg protocol: 328 ± 123.8, after 20 mg protocol: 555 ± 378.8 (pg/mL, mean ± standard deviation), p = 0.0008]. There was a significant difference between the gastric emptying breath test Tmax at baseline and just after the 20 mg protocol (baseline: 45.5 ± 15.3, after 20 mg protocol: 60.5 ± 19.6 min, p = 0.0418). Plasma desacyl-ghrelin levels increased significantly just after the 20 mg protocol compared to those at baseline [baseline: 222.3 ± 106.4, after 20 mg protocol: 366.2 ± 178.6 (fmol/mL), p = 0.0008]. Conclusions: In healthy adults, 14 days of vonoprazan fumarate administration at 20 mg/day delayed gastric emptying. Trial registration: This clinical trial was registered in the University hospital Medical Information Network Clinical Trial Registry (Trial No. UMIN000039199 and UMIN000042969). [ABSTRACT FROM AUTHOR]

The Fukushima-Daiichi Nuclear Power Plant (FNPP) accident in March of 2011 released substantial amounts of radionuclides into the environment. We collected 4,957 deciduous teeth formed in children before the Fukushima accident to obtain precise control data for teeth formed after the accident. Radioactivity was measured using imaging plates (IP) and epidemiologically assessed using multivariate regression analysis. Additionally, we measured 90Sr, 137Cs, and natural radionuclides which might be present in teeth. Epidemiological studies of IP showed that the amount of radioactivity in teeth from Fukushima prefecture was similar to that from reference prefectures. We found that artificial radionuclides of 90Sr and 137Cs, which were believed to have originated from past nuclear disasters, and natural radionuclides including 40 K and daughter nuclides in the 238U and 232Th series contributed to the generation of radioactivity in teeth. We also found no evidence to suggest that radionuclides originating from the FNPP accident significantly contaminated pre-existing teeth. This is the first large-scale investigation of radioactivity and radionuclides in teeth. The present findings will be indispensable for future studies of teeth formed after the FNPP accident, which will fall out over the next several years and might be more contaminated with radionuclides. [ABSTRACT FROM AUTHOR]

Ultraflexible optical devices have been used extensively in next-generation wearable electronics owing to their excellent conformability to human skins. Long-term health monitoring also requires the integration of ultraflexible optical devices with an energy-harvesting power source; to make devices self-powered. However, system-level integration of ultraflexible optical sensors with power sources is challenging because of insufficient air operational stability of ultraflexible polymer light-emitting diodes. Here we develop an ultraflexible self-powered organic optical system for photoplethysmogram monitoring by combining air-operation-stable polymer light-emitting diodes, organic solar cells, and organic photodetectors. Adopting an inverted structure and a doped polyethylenimine ethoxylated layer, ultraflexible polymer light-emitting diodes retain 70% of the initial luminance even after 11.3 h of operation under air. Also, integrated optical sensors exhibit a high linearity with the light intensity exponent of 0.98 by polymer light-emitting diode. Such self-powered, ultraflexible photoplethysmogram sensors perform monitoring of blood pulse signals as 77 beats per minute. Flexible electronic devices remain an attractive technology for optical sensor applications that require long-term health monitoring and conformability on human skin. Here, the authors report an ultrathin self-powered integrated organic optical system for plethysmogram monitoring. [ABSTRACT FROM AUTHOR]

We define a tracial analog of the notion called a sequentially split ∗ -homomorphism between C ∗ -algebras due to Barlak and Szabó and show that several important approximation properties related to the classification theory of C ∗ -algebras pass from the target algebra to the domain algebra. Then, we show that this framework arises from tracial Rokhlin properties of a finite group action and an inclusion of unital C ∗ -algebras. [ABSTRACT FROM AUTHOR]

TUBB4A gene variants cause dystonia type 4 and hypomyelination with atrophy of the basal ganglia and cerebellum. We report the case of a child with delayed motor development, intellectual disability, and dystonia. Magnetic resonance imaging revealed hypomyelination and progressive cerebellar atrophy without atrophy of the basal ganglia. Whole-exome sequencing revealed a de novo heterozygous variant, c.1088T > C, p.(Met363Thr), in TUBB4A. The present case further supports the vulnerability of the cerebellum in patients with TUBB4A pathogenic variants. [ABSTRACT FROM AUTHOR]

Neuroligin 3 (NLGN3) and neurexins (NRXNs) constitute a canonical transsynaptic cell-adhesion pair, which has been implicated in autism. In autism spectrum disorder (ASD) development of sociality can be impaired. However, the molecular mechanism underlying NLGN3-mediated social development is unclear. Here, we identify non-canonical interactions between NLGN3 and protein tyrosine phosphatase δ (PTPδ) splice variants, competing with NRXN binding. NLGN3-PTPδ complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPδ and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPδ interaction is impaired exhibit impaired social behavior and enhanced motor learning, with imbalance in excitatory/inhibitory synaptic protein expressions, as reported in the Nlgn3 R451C autism model. At neuronal level, the autism-related Nlgn3 R451C mutation causes selective impairment in the non-canonical pathway. Our findings suggest that canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality. Mutations of Neuroligin 3 (NLGN3) have been associated with autism spectrum disorder (ASD). Here, the authors identify a previously undescribed interaction between NLGN3 and a splice variant of protein tyrosine phosphatase δ (PTP δ) and its role in development of social behaviour in mice. [ABSTRACT FROM AUTHOR]

Background: Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare. Case presentation: We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy. Conclusions: GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient. [ABSTRACT FROM AUTHOR]

Introduction: Pigment epithelium-derived factor (PEDF) may play a role in cardiometabolic disorders. The aim of this study was to investigate which biochemical and clinical parameters are independently associated with serum PEDF levels in patients with type 2 diabetes mellitus (T2DM). Methods: We performed a cross-sectional analysis of 124 patients with T2DM who underwent continuous glucose monitoring (CGM) and blood chemistry analysis, including the diacron-reactive oxygen metabolites (d-ROMs) test and serum PEDF measurement (study 1). Then we investigated whether the changes in the studied biochemical and clinical parameters after 24 weeks of treatment (Δparameters) with anti-hyperglycemic agents, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and/or insulin and anti-hypertensive drugs and statins, were independently correlated with change in PEDF (ΔPEDF) in 52 of the patients with T2DM for whom there was sufficient serum samples to perform the post-treatment analysis (study 2). Serum levels of PEDF were measured with an enzyme-linked immunosorbent assay. CGM metrics were calculated on days 2 and 3. Oxidative stress was evaluated using the d-ROMs test. Results: Body mass index (BMI), triglycerides, fasting C-peptide, mean amplitude of glycemic excursions (MAGE), urinary albumin-to-creatinine ratio (UACR), and d-ROMs were positively associated with serum PEDF level, and high-density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) were inversely associated with serum PEDF level. Because these parameters were correlated with each other, multivariate stepwise analysis was performed: eGFR, HDL-C, BMI, MAGE, and UACR remained significant (R2 = 0.452). Furthermore, ΔMAGE and Δd-ROMs were positively correlated with ΔPEDF in study 2. Conclusions: The results of this study suggest that MAGE may be independently correlated with elevations in serum PEDF level in patients with T2DM. [ABSTRACT FROM AUTHOR]

The ZIPANGU study assessed the efficacy and safety of ranibizumab as a one loading dose + pro re nata (one + PRN) regimen with/without focal/grid laser among treatment-naïve patients suffering from macular edema (ME) following branch retinal vein occlusion (BRVO). ZIPANGU was a phase IV, prospective, randomized, open-label, active-controlled, 12-month, two-arm, multicenter study. Treatment-naïve patients with visual impairment (19–73 letters) caused by ME, defined as central subfield thickness (CSFT) > 300 µm, due to BRVO were randomly assigned to ranibizumab monotherapy (n = 29) or combination therapy (ranibizumab + focal/grid short-pulse laser, n = 30). The primary endpoint was the number of ranibizumab injections. Secondary endpoints were mean changes in best-corrected visual acuity (BCVA) and CSFT, and safety. There were no statistically significant differences in the mean number of ranibizumab injections between monotherapy (4.3 injections) vs. combination (4.1 injections) therapy, or in CSFT. BCVA improvement in the monotherapy arm (22.0 letters) was better than the combination therapy arm (15.0 letters) (p = 0.035). Overall, both regimens appeared to be safe and well tolerated. One + PRN ranibizumab is safe and efficacious in treatment-naïve patients with ME secondary to BRVO. A conjunctive laser treatment did not lead to better functional outcomes or fewer ranibizumab injections. [ABSTRACT FROM AUTHOR]

A bounded linear operator T : H1 → H2, where H1,H2 are Hilbert spaces, is said to be norm attaining if there exists a unit vector x ∈ H1 such that ||Tx|| = ||T|| and absolutely norm attaining (or AN-operator) if T/M: M ∈ H2 is norm attaining for every closed subspace M of H1. We prove a structure theorem for positive operators in β(H) := {T ∈ B(H) : T/M : M ∈ M is norm attaining for all M ∈ RT }, where RT is the set of all reducing subspaces of T. We also compare our results with those of absolutely norm attaining operators. Later, we characterize all operators in this new class. [ABSTRACT FROM AUTHOR]

Reports of early and catastrophic acute structural valve deterioration (SVD) in Trifecta valve (Abbott, St Paul, MN, USA) with multiple leaflet detachment are rare. We encountered two cases of early SVD in Trifecta valve with tears on two leaflets. Both cases presented with acute heart failure because of aortic insufficiency, and underwent redo aortic valve replacement; one patient died due to multiple organ failure caused by cardiogenic shock. Durability issues with the Trifecta valves; thus, necessitates long-term vigilance in aortic replacement patients. [ABSTRACT FROM AUTHOR]